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Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520
Lupus-prone mice develop a systemic autoimmune disease that is
dependent upon the B cell help provided by autoreactive 
ß
CD4+ T cells. Since autoreactive T cells with high affinity
for self peptides are normally deleted in the thymus, their presence in
these mice suggests the possibility that intrathymic negative selection
may be defective. Here, we directly compared central T cell tolerance
in response to a conventional peptide Ag in lupus-prone MRL/MpJ
mice with a nonautoimmune strain using an MHC class II-restricted TCR
transgene. Our results did not demonstrate any defects after Ag
exposure in the induction of intrathymic deletion of immature
CD4+CD8+ thymocytes, in TCR down-regulation, or
in the number of apoptotic thymocytes in MRL/MpJ compared with
nonautoimmune mice. Furthermore, we found that the lpr
mutation had no influence upon the Ag-induced thymic deletion of
immature thymocytes. These data support the notion that T cell
autoreactivity in MRL/MpJ mice is caused by defects in peripheral
control mechanisms.
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